KRAS and colorectal carcinoma: As PFKFB3 protein expression levels do not always show a direct correlation to 3PO response (Supplementary Fig. S1B, immunoblot with CRC cell lysates), additional reasons for this phenotype upon 3PO treatment might be related with the intrinsic metabolic needs, directly dictated by the mutational status (TP53 mutation; KRAS mutation; CpG island methylated phenotype) and by its transit-amplifying undifferentiated phenotype, which could also influence its susceptibility to 3PO (32, 33).